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  • 1
    ISSN: 1619-7089
    Keywords: Radioimmunoscintigraphy ; Antibody localisation ; Circulating antigen ; Rat model ; Immune complex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of circulating antigen (human kappa light chains (LC)) on radioimmunoscintigraphy was examined in a normal rat model. Rats were implanted subcutaneously with kappa (test) and lambda (control) LC coupled to sepharose beads (500 μg LC/ml swollen gel). When 131I-labelled monoclonal antibody, K-1-21 was injected, clear images of specific antibody localisation to the kappa implant were seen 6 days later. The kappa implant: blood ratio (K:B) was 7.69±0.45, which represented an implant uptake of 2.52±0.20 percent injected dose per gram (%ID/g). When 131I-K-1-21 was preincubated with 125I-kappa LC at ratios of up to 1:10 antibody: antigen, (w/w) before injection; or if antigen was given daily by bolus injection or continuously infused via an osmotic pump, very clear specific images of antibody localisation to the kappa implant were still obtained. There was, however, a decline in the absolute uptake of label by the kappa implant. The greatest change was observed following continuous antigen infusion, when kappa implant uptake fell to 1.26±0.1 %ID/g. Nevertheless, the K:B ratio was still maintained at 6.8±0.2, due to increased clearance of antibody from the blood. Thus, in this case, where antigen and antibody might be expected to form small, soluble immune complexes, there was no major deleterious effect on radioimmunoscintigraphy.
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  • 2
    ISSN: 1619-7089
    Keywords: Radionuclide gated heart pool scan ; Diastole ; Peak filling rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Abnormal left ventricular diastolic function is being increasingly recognised in patients with clinical heart failure and normal systolic function. A simple routine radionuclide measure of diastolic function would therefore be useful. To establish this, the relationship of peak diastolic filling rate (normalized for either end diastolic volume, stroke volume, or peak systolic emptying rate), and heart rate, age, and left ventricular ejection fraction was studied in 64 subjects with normal cardiovascular systems using routine gated heart pool studies. The peak filling rate, when normalized to end diastolic volume, correlated significantly with heart rate, age and left ventricular ejection fraction, whereas normalization to stroke volume correlated significantly to heart rate and age but not to left ventricular ejection fraction. Peak filling rate normalized for peak systolic emptying rate correlated with age only. Multiple regression equations were determined for each of the normalized peak filling rates in order to establish normal ranges for each parameter. When using peak filling rate normalized for end diastolic volume or stroke volume, appropriate allowance must be made for heart rate, age and ejection fraction. Peak filling rate normalized to peak ejection rate is a heart rate independent parameter which allows the performance of the patient's ventricle in diastole to be compared with its systolic function. It may be used in patients with normal systolic function to serially follow diastolic function or if age corrected, to screen for diastolic dysfunction.
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  • 3
    ISSN: 1619-7089
    Keywords: Scintigraphy ; Monoclonal antibody ; Gamma camera imaging ; Clots ; Fibrin ; Rabbit model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The detection of thrombi in rabbits has been investigated with131I-labelled DD-3136/22, a monoclonal antibody (Mab) reactive at high affinity (Kd=2.68 x 10−10 M) with human D Dimer (DD). DD-3136/22 bound well to both “fresh” and “aged” human clots in an in vitro assay but showed poor binding to rabbit clots. However, reactivity was restored to rabbit blood if it was seeded, before clotting, with human DD covalently coupled to Sepharose beads. Thus, a rabbit model was developed in which blood was allowed to clot around DD-Sepharose beads introduced into the jugular vein. Gamma camera imaging showed that intact131I-labelled DD-3136/22 localised to these clots within 24 h. Uptake at this time was 0.202±0.012% injected dose per gram (%ID/g) compared with 0.086±0.018%ID/g after injection of control antibody.131I-labelled F(ab′)2, fragments of DD-3136/22 allowed earlier scintigraphic detection of the clot which was evident 4 h after injection. Uptake in the clot at 24 h was 0.154±0.038 %ID/g compared with 0.109±0.027 %ID/g for a control F(ab')2. As antigen levels in the clot are estimated to be less than 300 μg DD, thus representing a very small human clot, the DD-3136/22 Mab would appear to have a good potential for the sensitive detection of thrombi in a clinical setting.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1619-7089
    Keywords: Monoclonal antibody ; 131I labelling immunoscintigraphy ; Myeloma ; Rat model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A novel experimental model was established in normal rats for studying the localisation and tissue distribution of a murine monoclonal antibody directed against kappa light chain B cell malignancies. The antibody, K-1-21 was raised against human kappa Bence Jones Proteins and reacts with a cell membrane antigen KMA which is restricted to some kappa myeloma and lymphoma cells. In the rat model, kappa or lambda Bence Jones protein-conjugated sepharose was implanted subcutaneously on either flank 24 h before the injection of 131I-labelled K-1-21 or its F(ab′)2 fragment. Gamma camera imaging and tissue distribution studies showed specific localisation of the K-1-21 antibody in the kappa sepharose. Injection of F(ab′)2 antibody fragments resulted in faster background clearance, earlier delineation of the specific image and significantly higher target to blood ratios than those obtained with the intact antibody. These results suggest that the model may provide an alternative system to tumour xenograft bearing nude mice for studying localisation of antibodies with therapeutic potential.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1619-7089
    Keywords: Gallium 67 scanning ; Lymphoma ; Hodgkin's disease ; Non-Hodgkin's ; Instrumentation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gallium 67 scanning in the malignant lympho mas has been done, with variable success, for over 20 years. After initial enthusiasm, the technique fell into disrepute and it was not until the early 1980s that it enjoyed a revival. There have been many major contributions to the literature, both favourable and unfavourable. The reasons for the latter include: poor instrumentation (only single-pulse height analysis), low gallium 67 doses, impatient and careless scanning techniques, timing of the study after treatment (chemotherapy, radiation) and insensitive methods of confirmation of the presence or absence of disease (“truth”). Anatomical diagnostic techniques (computed tomography, plain X-radiography, magnetic resonance imaging and others) are incapable of distinguishing viable tumour in normal size lymph nodes or necrotic/fibrotic residual masses. With improvements in instrumentation (triple-pulse height analysis, gamma camera resolution and tomographic techniques) gallium 67 can detect active tumour in residual masses and in normal-size nodes. This is due to gallium 67's unique ability to localize in viable tumour cells. It has greater than 90% sensitivity, specificity, accuracy and positive predictive value in patients with lymphoma. Its major contributions are in: staging (changing management of mediastinal disease, obviating the need for a laparotomy and clearlyidentifying stage IV disease); detecting relapse or residual, progressive disease (it establishes true complete remission and is often the first and only evidence of relapse before clinical evidence); predicting response to therapy (failure to convert to a negative scan post-treatment signals a poor prognosis and alternative therapy is required); and predicting outcome — prognosis (it is the only diagnostic modality to predict outcome accurately).
    Type of Medium: Electronic Resource
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